Energy-efficient solvent-free method for producing metal chelates

ABSTRACT

The invention relates to a method for producing, amongst other things, amino-acid and/or hydroxycarboxylic-acid metal chelates, a solvent-free mixture of at least one metal oxide, metal hydroxide, metal carbonate or oxalate, and the solid organic acid is subjected to intensive mechanical stress. According to the invention, this is done in that the reaction partners are introduced in particle form into a fluid stream of a fluid-bed countercurrent mill operating without grinding elements, wherein mechanical activation of at least one of the reaction partners is effected by collision processes within a reaction chamber formed in a region of the fluid stream, and a solid body reaction to form the metal chelate is triggered. The novel method operates very energy-efficiently and with a high specific yield. It leads to a product having compact particles in the small, single-digit micrometer range having a comparatively narrow particle sizc distribution and a large surface. The product is homogenous and very pure. Thermal loading or decomposition of the organic chelate ligands, in particular of the amino acids, is likewise avoided, as are contaminants from milling and grinding element abrasion.

The invention relates to the efficient preparation of metal chelates, inparticular amino acid-metal chelates and hydroxycarboxylic acid-metalchelates, in which a dry, namely solvent-free, mixture of at least onemetal compound from the group consisting of metal oxide, metal hydroxideand metal salt and at least one solid organic acid which comprises atleast one chelating acid from the group consisting of alpha- andbeta-amino acids and hydroxycarboxylic acids is subjected to intensivemechanical stress in order to produce the chelate complexes mentioned.The invention further relates to the corresponding metal chelatecompositions as are obtainable by means of this process, the use thereofand also further compositions which contain the process product or themetal chelate compositions according to the invention.

Chelates or synonymously chelate complexes are coordination compounds inwhich at least one polydentate ligand, hereinafter referred to aschelating ligand or “chelator”, occupies at least two coordination orbonding positions on a central atom. In a chelate complex, one or morechelators can be present per central atom. The central atom is apositively charged metal ion of metals such as, inter alia, zinc (Zn),copper (Cu), manganese (Mn), selenium (Se), iron (Fe), calcium (Ca),magnesium (Mg), nickel (Ni), cobalt (Co), vanadium (V), chromium (Cr)and molybdenum (Mo). In the chelate, some metals occur as cations inonly one valence (e.g. Zn²⁺) while others (e.g. those of Cu, Fe, Ni, Co,V, Cr or Mo) occur in a plurality of valences or as oxo cations, forexample molybdenum oxo cations in the oxidation states +IV, +V and +VIand vanadium usually in the form of vanadyl, VO²⁺.

It has been known for a long time that trace elements and trace elementcompounds are present in small amounts (“in traces”) in animal, human orvegetable organisms and often fulfill functions which are important tolife, which can be seen from the fact that a deficiency of them leads tomanifestation of deficiency or disease symptoms, to general weaknessand/or to a reduced reproduction rate. Being able to supply theseelements in a suitable administration form is therefore of greatinterest.

Using one (or more) organic acid anions which contain additionalelectron donor groups (—NH₂, —OH), in particular amino acid anions, aschelate complex partners of the respective metal and thus utilizing, inaddition to the trace element, the amino acids and/or hydroxycarboxylicacids which are in any case frequently administered as supplements withtheir positive physiological action in the form of a slightlybioavailable complex is also known and is customary practice (see, forexample, K. W. Ridenour, U.S. Pat. No. 5,702,718 (A), 1997 and patentscited therein).

In general, not only natural amino acids but any organic acids bearingamino and/or hydroxy groups, preferably with these substituents in thealpha or beta position relative to the carboxyl unit, are generallysuitable for preparing these metal chelates. However, preference isgiven to using the naturally occurring amino acids alanine, arginine(basic), aspartene, aspartic acid (acidic), cysteine, glutamine,glutamic acid (acidic), glycine, histidine (basic), isoleucine, leucine,lysine (basic), methionine, phenylalanine, proline, serine, threonine,tryptophan, tyrosine and valine.

A suitable method for preparing such compounds, which are widely used,for example as additives in the human sector and in animal nutrition, isof great general interest. The chelate stability should not have anadverse effect on the bioavailability of the amino acid orhydroxycarboxylic acid. Many amino acid chelates even increase thebioavailability of the central cation coadministered compared to a saltor oxide of this cation.

As has now been shown by scientific studies, bioresportion fromparticular chelate compounds in the human or animal organism isparticularly effective. The amino acid chelates with their moderatestrength of chelating via the nitrogen atom display a particularly highbioavailability. As is well documented in the literature and known tothose skilled in the art, a significantly higher bioavailability of themetals has often been found when they are used in the form of theirchelates than is the case when using corresponding inorganic metalsalts.

According to the present-day state of the art, the production ofsuitable amino acid-metal chelates as organic trace element compounds ismainly carried out with only low energy efficiency by wet chemical meansor else by likewise energy-intensive mechanical processes withparticipation of milling media, especially in ball mills, within thelatter case about 90% of the energy supplied being merely converted intoheat (see EP 2489670 A1). The known wet-chemical processes are burdenedby, in particular, the unavoidably energy-inefficient andcorrespondingly costly drying of the material; in addition, the productis not free of foreign inorganic anions.

Solvent-free processes, inter alia, are also known from the prior art(Rummel, U.S. Pat. No. 2,877,253 (A), 1959; Ashmead, Pedersen, U.S. Pat.No. 6,426,424 (B1), 2002; Pedersen, Ashmead, U.S. Pat. No. 6,518,240(B1), 2003). Although solvent-free processes do not per se have theabovementioned disadvantage that large amounts of the solvent, normallywater, have to be removed, they do however require additional amounts ofenergy when product formation occurs in mechanical mills containingmilling media, especially in ball mills. The reason for the increasedenergy consumption is that milling media have to be set in motion asadditional masses, for example in the process described by D. Ramhold,E. Gock, E. Mathies, W. Strauch, EP 2489670 (A1), 2012, in an excentricvibratory mill (EVM). When excentric vibratory mills are used, theenergy consumption for driving the counterweight is additional.Furthermore, in such an inhomogeneously operating vibratory mill system,comparatively high wear is observed as a result of the high impactstresses on the milling media themselves. The abraded material is thenundesirably found in the product.

In addition, the drying of material mentioned at the outset also becomesrelevant in the last-named processes since water of reaction formed inthis type of reaction milling has to be removed again under action ofheat and/or with reduction of the pressure, with additional energyconsumption.

A further disadvantage of the abovementioned solid-state processes forproducing metal chelates is the sometimes considerable sizeheterogeneity and structural heterogeneity of the solid productsobtained. Thus, for example, the process described in EP 2 489 670 A1produces acicular metal-amino acid chelate structures having an averageparticle size of from 40 to 60 μm, with up to 80% of the particleshaving a particle size from >0 to 100 μm and up to 2% have a particlesize of more than 500 μm, i.e. a value which is a factor of 10 higherthan the “average size” of 50 μm, thus with a considerable amount ofoversize particles.

A great structural heterogeneity quite generally increases thedifficulty of further processing of the metal chelate complexesobtained, for example classification according to particle size, precisemetering and homogeneous mixing with further substances. The activecompound release kinetics are also unfavorably influenced by theparticle size heterogeneity. A greatly acicular morphology hinders theflowability and scatterability of the particulate product. Acicularcrystals of the complexes with are not readily water-soluble andsometimes even acid-insoluble can be hazardous to health when absorbedin the human or animal body. Acicular structures are therefore to beavoided.

It is therefore an object of the invention to avoid the disadvantages ofthe prior art in respect of the production process as far as possibleand to provide metal chelates having a different morphology. Anenergy-efficient process giving a good yield and having a highselectivity should be made available here. By-products and decompositionproducts, in particular of the organic complexing ligands, should beavoided.

The starting materials for the process are present in the solid state.The nature of the particles of the starting materials can correspond toa finely particulate or finely crystalline, commercial form normal forthe material. Premilling of the starting materials is generally notnecessary. The metal oxides used, e.g. zinc oxide and copper oxide, areavailable with particle sizes in the range from, for example 150 to 300μm and can be used in this form. The solid organic acids arecommercially available with particle sizes of from about 200 to 500 μmand can likewise be used directly as obtained, i.e. in commercialparticle sizes.

To provide the central atom, metal compounds selected from the groupconsisting of: metal oxides, metal hydroxides, including mixed oxidesand mixed hydroxides, inorganic metal salts and organic metal salts areused. For the chelate ligands, i.e. as chelating organic acids, use ismade of amino acids and/or hydroxycarboxylic acids. Further ligandswhich are not bidentate can be included. The starting materials can beused in premixed form or they can be introduced individually into thefluidized-bed opposed-jet mill serving as reactor and be mixed in aseparate apparatus or directly in the milling space of the mill. Metaloxides, metal carbonates and metal oxalates are preferred as metalcompound.

According to the invention, the reactants, i.e. at least the metalcompound used and the organic acid, are introduced in particulate forminto a fluid jet of a fluidized-bed opposed-jet mill operating withoutmilling media. It is important that all reactants are fed into acollision zone in the milling space in which sufficient excitation ofthe reactants and the activation energy for the desired complexingreaction are provided by particle-particle impacts in the milling gasjet and especially in the center of these nozzle jets. This occursduring use according to the invention of the fluidized-bed opposed-jetmill primarily in the same zone in which the “milling” (here “jetmilling”), i.e. the comminution of the solid particles which mayadditionally take place here too, takes place in the conventional use.The milling space comprises the reaction zone and forms a reaction spacefor the reactive milling or reaction milling taking place here. Theprocess can be carried out continuously by continuously feeding in thereactants. The fluidized-bed opposed-jet mills to be used require notonly far less energy than mills using milling media but also less energythan conventional jet mills in which the milling stock is introducedtogether with the milling gas stream into the milling space andfrictional processes between milling stock and mill wall take place. Inaddition, the fluidized-bed opposed-jet mill therefore operatesvirtually without wear (in contrast to classical ball mills and also toa conventional jet mill).

In summary, it may be said that mechanical activation of at least one ofthe reactants is brought about by particle collision processes within areaction space formed in a jet region of the fluid jet or a plurality offluid jets, and a solid-state reaction to form the metal chelate istriggered.

The process is based on acceleration of particles by means of a millinggas stream at high pressure and subsequent collision of these particles,in particular in the focus of milling gas jets directed toward oneanother. The corresponding collisions lead to such a high energy inputthat the respective organic acid and the metal source used react to forma chelate.

Here, the oxygen of the metal component forms pure water which at thehigh air speeds of the process is discharged together with the millinggas stream. Accordingly, no additional energy has to be expended forthis purpose.

As regards product formation, it is assumed that the particlecollisions, particularly in the center of the gas jets, triggered by jetvelocities of usually from 300 m/s to 1000 m/s, lead to lattice defectsresulting from the point loadings described. Even at room temperatureand a gauge pressure of 6 bar, milling gas velocities of 500 m/s areattained. The abovementioned lattice defects are probably presentprimarily in the metal compound used having a high specific gravity andmake the subsequent reaction to form the amino acid-metal chelatepossible. Prior energy-intensive activation, as in the case ofcorresponding reaction milling processes in an excentric vibratory mill(e.g. as described by D. Ramhold, E. Gock, E. Mathies, W. Strauch, EP2489670 (A1), 2012), is not necessary, which means a further energysaving. High values of the indicated milling gas velocities, with acorresponding advantage for the extent of particle-particle collisionsin the milling space of the fluidized-bed opposed-jet mill, are achievedparticularly when the milling gas, which is naturally obtained hot fromthe compressor, is not cooled with consumption of energy (as isotherwise customary) but instead is used directly as hot gas.

The metal chelate can be a “pure” chelate produced from one metalcompound and one amino or hydroxycarboxylic acid or a mixed product inthe case of which metal oxides of various metals and/or a plurality ofdifferent acids are used in admixture.

The product is collected in a product filter installed downstream of thefluidized-bed opposed-jet mill.

The disadvantages of the processes known from the prior art which aredisadvantageous from a process engineering and/or energy point of viewcan be avoided in this way. The invention is based on the recognitionthat fluidized-bed opposed-jet mills originally designed for very finemilling allow such a high energy input into the milling stock that, whenthe starting materials and operating conditions are chosenappropriately, a mechanochemical reaction occurs solely by collision ofparticles of the material with one another without participation ofmilling media or other frictional surfaces being necessary.

In contrast thereto, such a solid-state reaction is, in cases knownhitherto from the literature, triggered by collision with milling mediain ball mills (centrifugal mills, excentric vibratory mills, see, forexample, D. Ramhols, E. Gock, E. Mathies, W. Strauch, EP 2489670 (A1),2012). Mechanisms of such mechanochemical reactions are assumed to begenerally tremadous point loadings associated with high localtemperatures (see, for example, B. V. Boldyrev, K. Meyer,Festkörperchemie, VEB Verlag für Grundstoffindustrie, Leipzig, 1973; D.Margetic, V. Strukil, Mechanochemical Organic Synthesis, ElsevierScience Publishing Co. Inc., 2016). The temperature-sensitive organicligands, namely the amino acids and/or hydroxycarboxylic acids here, canbe subject to undesirable degradation reactions in such processes.

In the present case according to the invention, on the other hand, nomilling media are present. Since, correspondingly, no additional masseshave to be set in motion, considerable quantities of energy can be savedin this way. In addition, the resource-conserving process according tothe invention in a fluidized-bed opposed-jet mill has the advantage thatthe end product is free of corresponding abraded metal because of theabove-described absence of (steel) milling media. The organic ligandsare likewise subjected only to mild conditions. The tendency forsecondary and degradation reactions to occur within the ligands isdrastically reduced since no heat input occurs in the process, neitherfor a thermal reaction nor as a result of strong mechanical activationby means of the mass of milling media.

Since the process is carried in the absence of solvent, the associatedsolvent contamination is absent, both in the production process and inthe product. No thermal stressing of the product caused by hot dryingoccurs. The problematical industrial use of salt solutions is likewisedispensed with, as is the disposal of considerable amounts of residualsalts as coproducts. The process products are, due to the synthesis,preferably free of sulfur and sulfates and generally free of salt anionswhich are not required in the process.

According to the invention, use is made of a fluidized-bed opposed-jetmill in which the particle collisions take place in the center of aplurality of fluid nozzles directed toward one another. Here, anopposed-jet arrangement is any arrangement in which the opposed-jetprinciple is employed, regardless of the specific angle between thefluid nozzles or milling gas nozzles. The fluid nozzles or milling gasnozzles can preferably be arranged at an angle of from 180° to 60°relative to one another with the jets from the “opposed-jet nozzles”having to cross in order to create a collision space which according tothe invention is utilized as reaction space.

In a preferred embodiment, a fluidized bed which provides the reactionspace for chelate formation is formed in a fluid stream section in acrossing region of the jet direction of at least two fluid nozzlestogether with the particulate reactants introduced. From two to sixfluid nozzles operating in the opposed-jet mode are at presentconsidered to be preferred, more preferably from two to four fluidnozzles or milling gas nozzles.

In preferred embodiments, the fluidized-bed opposed-jet mill is operatedat flow velocities of from about 100 to 1000 m/s, preferably from 250 to1000 m/s, more preferably 300-1000 m/s, in particular from 300 to 700m/s, and a milling gas pressure of from about 5 to 10 bar, preferablyfrom about 7 to 8 bar.

The reactants provided at the inlet of the mill or for feeding into themill, i.e. the solid particulate metal hydroxide, metal carbonate ormetal oxalate and the solid amino and/or hydroxycarboxylic acid(s), arefed in as “reaction material” instead of the conventional pure millingstock. This preferably occurs, in general from one or more stock vessels(reservoir(s)), alternatively batchwise from sacks, by means of anindependent feed device, for example a shaft or a feed conduit with orwithout additional transport means.

The use of a fluidized-bed opposed-jet mill means that the reactionmaterial is introduced directly into the milling space; in this way, thegas introduced through the nozzles is itself kept free of particles ofthe starting material, which could otherwise cause wear and abrasionthere, as is the case in conventional jet mills as a result of transportof material through the nozzles and especially in classical mills usingmilling media (in particular ball mills).

In a particularly preferred embodiment, the reactants are transported bymeans of a transport device into the milling chamber and reach thereaction space in the interior of the milling chamber in free fall. Thetransport device preferably has at least one transport screw.

The particle size of the end product can be set by choice of theoperating conditions of the fluidized-bed opposed-jet mill together withthe classifier wheel which is usually also mounted as standard for veryfine milling, usually to the medium to small one-figure micron range(average diameter determined in the manner customary in the art, forexample by means of laser light scattering).

The process product is compact and finely particulated. The compactstructure is virtually free of crystal needles and there are noappreciable proportions of oversized particles. More than 80% of theparticles have an ellipsoidal or cuboidal structure in which the ratioof the longest to shortest particle diameter is less than 4:1. Owing tothe compact, finely particulate structure, there is furthermore acomparatively large surface area which has, for example, a positiveeffect on the scatterability or flowability of the product, the drymiscibility, the dispersibility and the metering accuracy and also thepharmaceutical properties, where appropriate, of products. The processproducts can thus be incorporated more readily into mixtures andcompacts and are more uniformly distributed in these.

The product is obtained in a particularly finely divided form with anarrow particle size distribution. The latter can, for example, be seenfrom the ratio of the D values, D₉₉, D₉₀, D₅₀, (D₁₀). The D valueindicates the percentage of particles smaller than the diameter given asthe respective D value. The percentage is given as index, i.e.: D₉₀= . .. means “90% of the particles have a (volumetrically determined)diameter of less than . . . ”. The associated data are obtained by meansof laser light scattering.

Compared to known energy-intensive solid-state processes using millingmedia, a particularly compact and homogeneous particle size is achieved.Thus, for example, the acicular chelate particles described in thepatent application EP 2389670 A1 and depicted in an electron micrographhave an average particle size of 40-60 μm, with up to 80% of theparticles being in the range 0-100 μm, which corresponds to a D80 valueof 100 μm. In comparison, in the case of the invention a very steep, farmore homogeneous and better defined particle size distribution isachieved and the particles are overall more than one order of magnitudesmaller with an average particle diameter of usually from 1.5 to 3.5 μm(instead of from 40 to 60 μm in the case of ESM processes, see above).This is advantageous for further process steps, in particular mixing ofdefined amounts of chelate with defined amounts of further substances,since a homogeneous particle size distribution makes processing bymachine considerably easier. The risk of lump formation is reduced, andthe mechanical components of classification, measuring, metering anddispensing plants can be better matched to a particular chelate crystalsize. Particular after-processing steps, e.g. milling of the chelatecrystals obtained to achieve a homogeneous, sufficiently small particlesize, can be dispensed with.

It is frequently the case that very small amounts of the metal-acidchelates are mixed with, for example, 1000 times their amount of othermaterials, e.g. in animal fodder or when used as catalyst. In order tobe able to add a defined amount of chelates and mix them homogeneouslywith other materials, a homogeneous, clearly defined particle size ofthe chelates is very advantageous.

The process product according to the invention is obtained in the formof compact crystals, i.e. virtually needle-free and without anappreciable proportion of oversized particles. When administered tohuman beings or animals, the harmful effects on health to be feared inthe case of the acicular chelate crystals obtained according to theprior art no longer occur.

It must be emphasized that the reaction milling according to theinvention in a fluidized-bed opposed-jet mill occurs completelyautogenously and in such a way that the entire energy for productformation including the necessary activation energy is providedexclusively by the gas jet. A temperature increase does not have to beeffected from the outside, nor does an uncontrolled temperature increase(which may possibly damage the product) take place in the materialsused, as is the case in classical reaction milling operations withongoing process, predominantly by impact and friction of the millingmedia themselves. Furthermore, the process of the invention has theadvantage that a fluidized-bed opposed-jet mill allows, in contrast toreaction milling in a classical ball mill, usually excentric vibratorymill, continuous operation of the process and thus an increasedthroughput at a lower specific energy consumption.

A comparative calculation of the respective specific energy consumptionin an excentric vibratory mill (single-module, ESM 504, from SiebtechnikGmbH, Mülheim an der Ruhr) and in a fluidized-bed opposed-jet mill (CGS71, from Erich NETZSCH GmbH & Co. Holding KG, Selb) is given in thefollowing section:

Excentric vibratory mill ESM 504:

Power (dry+mixer): 27.5 KW

Throughput: 40 kg/h

Milling media: Cylpeps 32 mm×32 mm (steel)

Specific energy consumption [KWh per metric ton]: 27.5 KW/40 kg/h×1000kg=688 KWh/t

Fluidized-bed opposed-jet mill CGS 71:

Air flow: 1920 m³/h (8 bar, 20° C.; ISO 1217)

Power for classifier wheel: 15 KW

Compressor power (1956 m³/h, main drive+sep. fan): 206 KW

Throughput: 500 kg/h

Specific energy consumption [KWh per metric ton]:

221 KW/500 kg/h×1000 kg=442 KWh/t

In contrast to the fluidized-bed opposed-jet mill, only batch operationis possible in the case of an excentric vibratory mill.

The specific energy consumption per metric ton of product in the case ofthe use according to the invention of a fluidized-bed opposed-jet millis thus more than one third below the consumption of a conventionalproduct plant for amino acid-metal chelates based on an excentricvibratory mill. Furthermore, the present process is characterized bydispensing with catalytically active reagents (such as iron ions) and(in terms of energy) avoiding complicated preceding or subsequentprocess steps (e.g. spray drying).

The invention thus now makes available an efficient solvent-free processfor preparing complexes of chelate-forming metals such as preferablyzinc, copper, manganese, selenium, iron, calcium, magnesium, nickel,cobalt, vanadium, chromium or molybdenum, preferably zinc, copper andselenium, with solid organic acids, preferably naturally occurring aminoacids, preferably glycine, methionine, lysine and/or cysteine, but alsoalanine, arginine, aspartene, aspartic acid, glutamine, glutamic acid,histidine, isoleucine, leucine, phenylalanine, proline, serine,threonine, tryptophan, tyrosine and valine. In general, allchelate-forming amino acids and/or hydroxycarboxylic acids, both ofsynthetic and natural origin, are suitable.

The reaction is achieved solely by a mixture of the respective metalcompound, preferably in the form of the oxides (in particular ZnO, CuO,Fe₂O₃, Mn₂O₃ or corresponding oxides of other metals desired for theproducts produced or else in the form of oxalates or carbonates of theselected metals for the compounds to be prepared, commixed with thesolid inorganic acid (preferably with participation of at least oneamino acid), as indicated above, being subjected to mechanical stress ina fluidized-bed opposed-jet mill.

The reaction conversion in the course of the mechanochemical solid-statereaction depends on the operating conditions relevant to the inventionin the fluidized-bed opposed-jet mill (i.e. on the milling gas flow andmilling gas pressure, on the type and temperature of the milling gas orfluid, preferably air, optionally also nitrogen, argon, carbon dioxideor steam, and on the classifier rotational speed and on the amounts ofstarting materials introduced). The entry velocity of the gasintroduced, thus in particular also geometry, dimensions and arrangementof the jet nozzles, and the degree of accumulation of the reactionmilling stock in the reaction chamber are also critical for occurrenceof the solid-state reaction.

Suitable fluidized-bed opposed-jet mills are, inter alia, standard inindustry for contamination-free comminution and have in principle beenknown for a long time (see, for example, P. M. Rockwell, A. J. Gitter,Am. Ceram. Soc. Bull. 1965, 44, 497-499). Since about 20 years ago, thedevelopment and optimization of such fluidized-bed opposed-jet millshave again been intensively researched (see, for example, P. B.Rajendran Nair, S. S. Narayanan, From World Congress on ParticleTechnology 3, Brighton, UK, Jul. 6-9, 1998 (1998), 2583-2595; M. Benz,H. Herold, B. Ulfik, Int. J. Min. Proc. 1996, 44-45, 507-519; Z. Korzen,R. Rink, A. Konieczny, Zeszyty Naukowe—Politechnika Lodzka, InzynieriaChemiczna i Procesowa 1997, 22, 141-150; H. Berthiaux, J. Dodds, PowderTechnol. 1999, 106, 78-87; H. Berthiaux, C. Chiron, J. Dodds, PowderTechnol. 1999, 106, 88-97). Fine or very fine milling frequently triesto get down to the one figure micron range, with application topharmaceutical products frequently being the main consideration inoptimization of the parameters (see, for example, P. W. S. Heng, L. W.Chan, C. C. Lee, S.T.P. Pharma Sciences 2000, 10, 445-451 or L. W. Chan,C. C. Lee, P. W. S. Heng, Drug Development Ind. Pharm. 2002, 28,939-947).

The considerable possible energy input is reflected for example, in thepossible comminution even of very hard materials including, for example,silicon carbide or aluminum oxide (Y. Wang, F. Peng, Part. Sci. Technol.2010, 28, 566-580; Y. Wang, F. Peng, Powder Technology 2011, 214,269-277; M. X. Zhang, H. Y. Chen, C. P. Yan, L. Y. Lin, Rev. Adv. Mat.Sci. 2013, 33, 77-84).

The actual course of a chemical reaction, characterized by the breakingand subsequent reformation of chemical bonds, and thus a reactionmilling under the operating conditions of fluidized-bed opposed-jetmills has previously never been utilized in the manner of the invention.An example of surface modification of ZnO nanoparticles may be found in:X. Su, Z. Cao, Q. Li, Z. Zhang, J. Adv. Microscopy Res. 2014, 9, 54-57and in: X. Su, S. Xu, T. Cai, Guangzhou Huagong 2012, 40, 101-102, bothon the subject of “jet grinding/jet milling” and surface modification.

The invention leads to process products having new, hithertounattainable product properties and encompasses a structurallyhomogeneous product which is novel in this form and has a very narrowparticle size distribution. The finely particulate nature of the productis also worthy of particular emphasis.

The object of the invention is accordingly also achieved by a metalchelate composition containing at least one metal chelate compoundhaving a polyvalent metal cation and at least one chelate ligand whichcomprises at least one chelating acid from the group consisting ofalpha- and beta-amino acids and hydroxycarboxylic acids, wherein thecompound is present in the form of particles having a particle size inthe one-figure micron range, i.e. an average particle diameter of 5 μm(D₅₀=1 to 5 μm), as described above in connection with the process.

The metal chelate composition contains at least one metal chelatecompound or consists thereof.

The invention encompasses metal chelate compounds which are obtaineddirectly as process products from the process of the invention, i.e. thepure metal chelate compounds formed on the basis of the stoichiometriccomposition of the starting materials, and also comprises compositionswhich contain not only these metal chelate compounds but also othermaterials which can be first and foremost residual starting materials orbe additives or further materials which supplement the composition andhave been introduced into the mill during the process.

The metal chelate compound is a coordination compound (also referred toas complex compound, complex) as described above having at least onecentral atom formed by a polyvalent, i.e. at least divalent, metalcation and at least one chelate ligand which comprises at least oneorganic, chelating, i.e. at least bidentate in respect of complexation,organic acid selected from the group consisting of alpha- and beta-aminoacids and hydroxycarboxylic acids. The amino acids can be natural aminoacids, in particular essential amino acids, or else bidentate syntheticamino acids.

The presence of other ligands in addition to the ligands specificallymentioned and claimed, namely other bidentate or monodentate ligandsand/or monovalent or polyvalent anions, in the metal chelate compound isnot ruled out according to the invention. This can, for example, bedesired in order to broaden the range of uses of the metal chelatecompositions of the invention.

A preferred complexing acid which can be incorporated in addition to atleast one amino acid or hydroxycarboxylic acid as ligand in the chelatecomplex is nicotinic acid. The associated products are aminoacid-nicotinic acid-metal chelates, e.g. copper-nicotinate-glycinate orselenium-nicotinate-methionate.

The metal chelate compounds and metal chelate compositions according tothe invention are dry, solid, particulate materials or products having acharacteristic structure and size distribution.

In particularly characteristic embodiments, the metal chelate compoundis present in the form of particles of which 90% have an averageparticle diameter (individual particle diameter) of not more than 15 μmand 50% have an average particle diameter (individual particle diameter)of not more than 5 μm (D₉₀≤15 μm; D₅₀≤5 μm). The average particlediameter (average over all particles in a sample) is in the range from 1μm to 5 μm for these embodiments.

Typical D₅₀ values for individual samples are in the range from 1.5 to4.5 μm.

Typical D₉₀ values for individual samples are in the range from 4 to 6μm. D₉₀ is preferably less than or equal to 15 μm and D₉₀ is morepreferably 7 μm. Typical D₉₉ values for individual samples are in therange from 8 to 15 μm. D₉₉ is preferably less than or equal to 20 μm andD₉₉ is more preferably 15 μm. There are no oversized particles based onthese values since the largest particles according to the invention havesizes which are still below 25 μm (D_(99.9)≤25 μm, equating or a sieveexclusion limit of <25 μm).

The particle size distribution of the process product according to theinvention is also significantly narrower than has been previouslyobtainable, as can be seen from FIG. 2 c . This clearly distinguishesthe product according to the invention from known wet-chemically ordry-chemically produced products.

Due to the finely particulate nature and the comparatively uniformparticle size, the metal chelate obtained by means of the process or themetal chelate composition according to the invention is readilymeterable, easier to scatter and free-flowing and readily able to be drymixed and dispersed. The fine microstructure can also have a positiveeffect on the resorbability of the products.

The metal chelate compound according to the invention is free of abradedmaterial from mills and milling media.

The metal chelate compound is preferably completely free of chlorideand/or sulfate ions as ligands.

The metal chelate composition is also preferably characterized in thatthe stoichiometric ratio (molar ratio) of chelating acid to metalcompound, in the case of a chelate mixture based on each individualchelate compound, is from 0.5:1 to 4:1. In particular embodiments, theor at least one metal chelate compound present in the metal chelatecomposition according to the invention is a 2:1 amino acid-metal chelatecompound, preferably of zinc or copper, or a 3:1 amino acid-metalchelate compound, preferably of iron or manganese.

As the analytical results reported below clearly show, the process ofthe invention makes it possible to obtain very well defined, chemicallypure chelates, as examined with the aid of the IR spectra of selectedmetal-amino acid 1:2 chelates. Since amino acid chelates areparticularly readily resorbable, or their constituents have aparticularly high bioavailability, the high conversion and the chemicalpurity in respect of this product is a very important quality advantageof the products according to the invention. In addition, the quality ismarked significantly by the absence of contamination of abraded metal,in particular since no milling media are used, and the particularmorphology of the product.

In general, a wide variety of central atoms can be selected. Inpreferred embodiments, the metal of the metal chelate compound or atleast one of the metal chelate compounds is selected from the groupconsisting of zinc (Zn), copper (Cu), manganese (Mn), selenium (Se),iron (Fe), calcium (Ca), magnesium (Mg), nickel (Ni), cobalt (Co),vanadium (V), chromium (Cr) and molybdenum (Mo).

In preferred embodiments, the chelating organic acid of the metalchelate composition according to the invention is selected from thegroup consisting of alpha-hydroxycarboxylic acids,beta-hydroxycarboxylic acids, natural amino acids, essential amino acidsand synthetic amino acids.

The metal chelates of the invention in particular encompass thefollowing substance types and substances: zinc bisglycinate, zincbislysinate, zinc bismethionate, copper bisglycinate, copperbislysinate, copper bismethionate, (selenium methionate, seleniumcysteinate), iron bisglycinate, iron trisglycinate, iron bislysinate,iron trislysinate, iron bismethionate, iron trismethionate, manganesebisglycinate, manganese trisglycinate, manganese bislysinate, manganesetrislysinate, manganese bismethionate, managanese trismethionate.

The metal chelates of the invention can be used in a conventional way.In particular, the following uses will be mentioned here: in a feedadditive, in a nutrient, as and in a nutrient supplement, as or in anutrient additive, as or in a medicament, as or in an antiseptic, in apharmaceutical composition, as or in a fermentation additive, asfertilizer additive, in a seed treatment agent, in a crop protectionagent, as catalyst for chemical reactions or in an electroplatingadditive. The invention accordingly also encompasses compositions forthe abovementioned uses, which have been prepared or formulated forthese uses and contain the process product of the process of theinvention, i.e. the metal chelate composition, as described in moredetail above.

WORKING EXAMPLES

The effect according to the invention of the mechanochemical stressingof metal oxides, metal carbonates or metal oxalates together with ineach case an organic acid, preferably amino acid, in a fluidized-bedopposed-jet mill will be illustrated below with the aid of a number ofexamples. Here, the reaction millings of the process of the inventionare carried out by way of example on a 2 to 22 kilogram scale. This doesnot represent a limitation. In principle, it is also possible to realizeconsiderably larger fluidized-bed opposed-jet mills as reactors forchelate production by modification of the dimensions, both for largerindividual amounts of material introduced and also for continuousoperation. Larger fluidized-bed opposed-jet mills for jet milling arealready industrially available. The working examples reported are for afluidized-bed opposed-jet mill from the manufacturer Hosokawa Alpine,Augsburg, having the designation AFG 100 and AFG 400, or from themanufacturer Netzsch, Hanau, having the designation CGS 10.

Working Example 1

1.501 kg of glycine (20.0 mol) and 0.814 kg of zinc oxide (10.0 mol) aremilled together for a time of 45 minutes in a fluidized-bed opposed-jetmill at an air flow of 50-80 m³/h, a milling gas pressure of 7.0 bar anda classifier rotational speed of 18 000 s⁻¹. An IR spectroscopicanalysis of the end product (FIG. 4 ) shows the virtually completeconversion of the amino acid mentioned (>95%) into the correspondingzinc glycinate (synonyms according to Chemical Abstracts Service CAS: a)bis(glycinato-N,O)zinc, b) bis(glycinato)zinc, c) glycine zinc salt, d)glycine, zinc complex, e) zinc bisglycinate, f) zinc glycinate, g)zinc(II) glycinate, h) zinc, bis(glycinato)). This IR spectrumcorresponds to that of a commercial reference, CAS: 14281-83-5).

Working Example 2

1.940 kg of methionine (13.0 mol) and 0.529 kg of zinc oxide (6.5 mol)are milled together for a time of 45 minutes in a fluidized-bedopposed-jet mill at an air flow of 50-80 m³/h, a milling gas pressure of7.0 bar and a classifier rotational speed of 18 000 s⁻¹. An IRspectroscopic analysis of the end product (FIG. 5 ) shows the virtuallycomplete conversion of the amino acid mentioned (>95%) into thecorresponding zinc methionate (Chemical Abstracts Number, CAS:40816-51-1).

Working Example 3

1.900 kg of lysine (13.0 mol) and 0.529 kg of zinc oxide (6.5 mol) aremilled together for a time of 45 minutes in a fluidized-bed opposed-jetmill at an air flow of 50-80 m³/h, a milling gas pressure of 7.0 bar anda classifier rotational speed of 18 000 s⁻¹. The end product zinclysinate is likewise obtained in a purity of >95%.

Working Example 4

1.576 kg of glycine (21.0 mol) and 0.835 kg of copper oxide (10.5 mol)are milled together for a time of 50 minutes in a fluidized-bedopposed-jet mill at an air flow of 50-80 m³/h, a milling gas pressure of7.0 bar and a classifier rotational speed of 18 000 s⁻¹. The end productcopper glycinate is likewise obtained in a purity of >95%.

Working Example 5

1.791 kg of methionine (12.0 mol) and 0.477 kg of copper oxide (6.0 mol)are milled together for a time of 55 minutes in a fluidized-bedopposed-jet mill at an air flow of 50-80 m³/h, a milling gas pressure of7.0 bar and a classifier rotational speed of 18 000 s⁻¹. The end productcopper methionate is likewise obtained in a purity of >95%.

Working Example 6

1.900 kg of lysine (13.0 mol) and 0.517 kg of copper oxide (6.5 mol) aremilled together for a time of 50 minutes in a fluidized-bed opposed-jetmill at an air flow of 50-80 m³/h, a milling gas pressure of 7.0 bar anda classifier rotational speed of 18 000 s⁻¹. The end product copperlysinate is likewise obtained in a purity of >95%.

Working Example 7

13.51 kg of glycine (180 mol) and 7.33 kg of zinc oxide (90 mol) aremilled together for a time of 4.5 minutes in a fluidized-bed opposed-jetmill at an air flow of 800-1200 m³/h, a milling gas pressure of 7.0 bar(80° C., uncooled compressor air) and a classifier rotational speed of4650 s⁻¹. Characterization of the corresponding zinc glycinate wascarried out by IR spectroscopy. The amount of product obtainedcorresponds to a throughput of 280 kg/h.

To better illustrate the invention, reference is made the accompanyingfigures. The figures show:

FIG. 1 a : a sectional view from the side of an in-principle sketch ofan apparatus for the reaction milling in a fluidized-bed opposed jetmill,

FIG. 1 b : a sectional view from above of an in-principle sketch of anapparatus for the reaction milling in a fluidized-bed opposed jet mill;

FIG. 2 a : scanning electron micrograph of zinc-glycine chelate (atleft),

FIG. 2 b : scanning electron micrograph of zinc oxide (at right),

FIG. 2 c : particle size distribution, measured on zinc bisglycinate,

FIG. 2 d : scanning electron micrograph of copper glycinate

FIG. 3 : ATR-IR spectrum of glycine;

FIG. 4 : ATR-IR spectrum of methionine;

FIG. 5 : ATR-IR spectrum of zinc-glycine chelate;

FIG. 6 : ATR-IR spectrum of zinc-methionine chelate;

FIG. 7 : ATR-IR spectrum of copper-glycine chelate.

FIGS. 1A and 1B show a schematic depiction of the reaction milling in afluidized-bed opposed-jet mill 10, with the sketches being limited tothe important elements of the apparatus. These are supplemented byapparatus elements which are not shown for starting material provisionand introduction, product discharge, instrumentation and the like.

The fluidized-bed opposed-jet mill depicted is of the type which iscommercially available and is used, for example, for very finecomminution of solids (milling, jet milling). In the example shown here,the mill is a fluidized-bed opposed-jet mill having a three-nozzlesystem.

FIG. 1 a schematically shows the apparatus, namely the fluidized-bedopposed-jet mill 10, in a sectional view from the side, while FIG. 1 bshows the same fluidized-bed opposed-jet mill 10 in a sectional viewfrom above, depicting the nozzle arrangement. Identical parts aredenoted by the same reference numerals.

As can be seen in FIG. 1 a , a milling chamber 1 is connected via a feedconduit 2 to a milling stock reservoir 3 from which the milling stock isfed into the milling chamber 1. In this working example, the solid,premixed reaction milling stock is introduced from the reservoir 3 infree fall and thus without additional energy input through the feedconduit 2 into the milling chamber 1 which provides or comprises areaction space 1 for the reaction milling according to the invention.

As an alternative, it would be possible to provide internals, forexample distributing internals, and also additional transport means inthe feed conduit 2, especially when introduction does not occur fromabove but instead, for example, from the side. Furthermore, it ispossible in alternative embodiments not shown here to keep the reactantsin stock in a plurality of separate reservoirs and mix them eitherimmediately before the milling chamber 1, which can occur in one of thefeed conduits 2 or in a separate mixing chamber, or to convey thereactants separately from the respective reservoirs and meter them intothe milling chamber 1, where the mixing can occur within the millingchamber itself.

The fluidized-bed opposed-jet mill 10 has at least two fluid nozzles 4which have to be directed toward one another or be arranged at an anglerelative to one another in order to generate a collision zone in thecenter of the nozzle arrangement.

As can be seen from FIG. 1 b , three fluid nozzles 4 for introduction ofthe milling jets are depicted in the example shown, with the nozzles orjet direction vectors crossing in a narrowly delimited zone where theparticles collide and subsequently react with one another. The fluidnozzles 4 are arranged in a plane perpendicular to the plane of thedrawing of FIG. 1 a and lie in the plane of the drawing of FIG. 1 b ,oriented at angles of 120° relative to one another in each case. Afluidized bed 5 composed of milling stock and gas is formed in thecenter of the nozzle arrangement, i.e. in a collision zone which isformed by means of the gas jets leaving the fluid nozzles 4.

The milling stock particles present in each case in the center of thefluid nozzles 4 directed toward one another within the fluidized bed andthe actual reaction space 5 formed thereby, here the reactants for thechelate formation reaction of the invention, are accelerated by the gasstream to such an extent that the chemical reaction and the associatedproduct formation is triggered after the particle collisions.

The actual reaction space 5 in which the solid-state reaction takesplace is located within the above-described collision zone in thefluidized bed.

FIG. 2 a shows a scanning electron micrograph of a sample of a zincglycinate (zinc bisglycinate) produced according to the inventioncompared to the zinc oxide (ZnO) used as starting material for the metalcompound in FIG. 2 b.

It can readily be seen that compact particles without a significantproportion of oversized particles, i.e. no needles as can be seen atright in FIG. 2 b for the zinc oxide starting material, are formed bymeans of the process of the invention. As a result, the product displaysbetter further processability and scatterability. The particle sizes arein a narrow one-figure micron range with a relatively narrow particlesize distribution. The product is therefore very homogeneous and has acomparatively high surface area. The product can therefore bedistributed readily, e.g. finely distributed in relatively complexcompositions, and metered, but also readily compacted. Since noundesirable foreign salts and by-products are present, the amino aciddensity and metal density in the product are high.

The particle size distribution of the zinc bisglycinate produced asdescribed in working example 1 and shown in FIG. 2 a was examined moreclosely by means of laser light scattering. The results are shown ingraph form in FIG. 2 c.

The overwhelming proportion of the particles has a diameter in the rangefrom about 1 to 4 μm. The narrow particle size distribution which can beread off from the individual diameter curve is reflected in typicalratios for the (volumetric) D10, D50 and D90 values.

99% of the particles have diameters of less than 10.00 μm (D₉₉),

90% of the particles have diameters of less than 6.82 μm (D₉₀),

50% of the particles have diameters of less than 3.41 μm (D₅₀) and

10% of the particles have diameters of less than 0.86 μm (D₁₀).

Further tests on other amino acid chelates according to the inventiongave D₅₀ values in the range from 1 to 5 μm. D₅₀ is therefore preferablyin the range from 1 to 5 μm, more preferably from 1.5 to 3.5 μm.

The D90 values are preferably in the range from 4 to 7 μm, and the D99values were less than 15 μm in each of the cases examined.

FIG. 2 d shows a scanning electron micrograph of a further productaccording to the invention, namely a copper bisglycinate produced asdescribed in working example 4.

The micrographs of the various amino acid chelates (for ZnGly₂ andCuGly₂) very clearly demonstrate that the process uniformly giveshomogeneous and finely divided amino acid chelates regardless of thestarting compound.

FIGS. 3 to 7 show infrared spectra which will be discussed in moredetail below.

Analytical Methods

In the case of the preparation according to the invention of aminoacid-metal chelates, the analysis of such compounds and thus the proofof the occurrence of a (mechano)chemical reaction is carried out bymeans of characteristic band positions, band shapes and band intensitiesin the infrared spectrum (IR), see, for example, H. Güdnzler, H.-U.Gremlich, IR-Spektroskopie, 4^(th) Edition, Wiley-VCH GmbH & Co. KGaA,Weinheim, 2003; G. Socrates, Infrared and Raman Characteristic GroupFrequencies: Tables and Charts, third edition, John Wiley & Sons, 2004;R. M. Silverstein, F. X. Webster, D. J. Kiemie, SpectrometricIdentification of Organic Compounds, John Wiley & Sons, Inc., 2005; J.Liu, Y. Hou, S. Gao, M. Ji, R. Hu, Q. Shi, J. Therm. Anal. Calorim.1999, 58, 323-330; M. Pedersen, H. D. Ashmead, U.S. Pat. No. 6,518,240(B1) 2003; J. J.-C. Ko, S. X.-J. Xie, EP 2204099 (A1) 2010. Thisanalysis is preferably carried out using the known technique ofattenuated total reflection, thus as ATR-IR. This procedure allowsdirect measurement of a sample without any sample preparation and thuswithout contamination with auxiliaries (for example potassium bromide inthe case of conventional sample preparation as KBr pellet) which couldin turn influence the measurement, e.g. by reducing the measurementresolution by band broadening or falsification of the band shape(Christiansen effect). The latter undesirable effect caused by aparticle size which is too large does not occur in the case of theproduct material produced according to the invention since this materialoccurs as compact particles in a small single-figure micron range with acomparatively large surface area (FIG. 2 a, d ).

The structural characterization of, for example, zinc bismethionate maybe found in R. B. Wilson, P. de Meester and D. J. Hodgson, Inorg. Chem.1977, 16, 1498-1502 or M. Rombach, M. Gelinky, H. Vahrenkamp, Inorg.Chim. Acta 2002, 334, 25-33. In the present case, too, it wasdemonstrated by means of such spectroscopic reference measurements thatthe products produced according to the invention are structurally thesame as wet-chemically-produced reference material, sometimescommercially available. This is emphasized particularly because the“American Association of Feed Control Officials” (AAFCO) define suchchelates as products of the reaction of a metal ion of a soluble metalsalt with an amino acid (see, for example, S. D. Ashmead, M. Pedersen,U.S. Pat. No. 6,426,424 (B1) 2002). In particular, the chelate formationwas demonstrated by significant changes in the IR spectrum during thecourse of the production process of the invention, which will beillustrated below with the aid of suitable examples.

ATR-IR Analysis, Spectroscopic Proof of Chelate Formation

In the course of IR analysis for the purpose of demonstrating thechelate formation when carrying out the process of the invention, thechange in position of the nitrogen-hydrogen stretching vibration NH ofthe ammonium group is of particular importance. This band is shiftedfrom about 3150 wave numbers (cm⁻¹, unit of the abscissa of the IRspectrum) in the case of the amino acid glycine (FIG. 3 ) or from lessthan 2950 cm⁻¹ in the case of methionine (FIG. 4 ) to about 3440 cm⁻¹for zinc glycinate (FIG. 5 ) or about 3295 cm⁻¹ for zinc methionate(FIG. 6 ) by chelate formation. The wave number differences which occurdemonstrate the participation of the nitrogen atom in complexation, thuschelate formation itself. Further bands in this region above 3000 cm⁻¹are essentially attributable to the presence of water ofcrystallization. In addition, harmonics of intense fundamentalvibrations of the upper fingerprint region are to be found there. Theasymmetric carboxylate stretching vibration v_(as)(COO⁻) of the aminoacids which is originally present appears at about 1575 cm⁻¹. Itsposition barely moves during the course of chelate formation. Theposition of the symmetric pendant of the carboxylate vibrationv_(sym)(COO⁻) also remains stable. Nevertheless, the formation of achelate in the course of the reaction according to the invention canalso be recognized unambiguously in this upper fingerprint region sinceonly in the case of the free amino acid is a deformation vibrationδ_(sym) (NH₃ ⁺) at about 1500 cm⁻¹ detected (e.g. δ_(sym)(NH₃ ⁺,glycine): 1498 cm⁻¹, δ_(sym)(NH₃ ⁺, methionine): 1514 cm⁻¹, δ_(sym) (NH₃⁺, lysine): 1511 cm⁻¹), but this disappears during the course ofreaction milling and chelate formation. The respective metal-nitrogenvibration in these chelates is found at only low wave numbers in thelower fingerprint region, e.g. Met-N (zinc methionate) at 419 cm⁻¹,because of the relatively high atomic masses of the metals. Thesignificant changes there in the IR spectrum of the metal chelatescompared to the corresponding spectra of the free amino acids arelikewise unambiguous evidence of chelate formation during the course ofthe process of the invention.

In the case of copper bisglycinate compared to the starting materialglycine, signals are present at about 3330, 3260 and 3160 cm⁻¹ in the IRregion of the chelate bands (cf. FIG. 7 ).

Summary of the Advantages of the Invention

The invention provides an energy-efficient process carried out in theabsence of solvent for preparing amino acid-metal chelates. Energysavings compared to previous processes arise firstly from the fact thatno wet-chemical reactions with subsequent drying are required. Althougha mechanochemical reaction is realized, no milling media and additionalmasses, for example counterweights in the case of reactions in excentricvibratory mills, are required, as otherwise in the prior art. Theprocess product is therefore kept free of abraded metal from the millingmedia. A mixture of the starting materials amino acid/hydroxycarboxylicacid and metal oxide, metal carbonate or metal oxalate fed in underatmospheric pressure is preferably converted mechanochemically into thecorresponding metal chelate solely by means of the fluid jet (gas jet)in a fluidized-bed opposed-jet mill due to the particle collisionsinitiated by the gas streams. The energy efficiency also arises from thefact that the process of the invention operates solely by means of themilling gas jet without additional introduction of thermal energy,radiative energy or the like being necessary. The autogenous reactionprocess which is therefore novel for complete chemical conversion of thestarting materials allows the combination of organic acids, preferablynaturally occurring amino acids such as glycine, methionine or lysine,with oxides, carbonates or oxalates of trace element metals, inparticular of zinc, copper, manganese, selenium, iron, calcium,magnesium, nickel, cobalt, vanadium, chromium or molybdenum.Sought-after fodder additives and nutritional supplements, e.g. zinc(bis)glycinate, zinc (bis)methionate, zinc (bis)lysinate, copper(bis)glycinate, copper (bis)methionate, copper (bis)lysinate and manymore, are obtained in this way. The use of hydroxycarboxylic acidsinstead of amino acids, which is likewise possible, leads first andforemost to food additives; other (industrial) uses of such chelatecompounds are known. The process product is obtained in verystructurally homogeneous and very pure form. Thermal stressing ordecomposition of the organic chelate ligands, in particular the aminoacids, is avoided as is contamination by abraded material from mills andmilling media.

In contrast to known processes using various mills, for exampleexcentric vibratory mills, the fluidized-bed opposed-jet mill also worksin continuous operation.

The water of reaction is removed together with the exiting milling gaswithout extra energy input.

LIST OF REFERENCE NUMERALS

-   -   10 Fluidized-bed opposed-jet mill    -   1 Milling chamber    -   2 Feed conduit    -   3 Milling stock reservoir    -   4 Fluid nozzle (milling gas nozzle)    -   5 Fluidized bed (reaction space)

The invention claimed is:
 1. A process for preparing amino acid- orhydroxycarboxylic acid-metal chelates, comprising: preparing asolvent-free mixture of at least one metal compound from the groupconsisting of metal oxide, metal hydroxide and metal salt, and at leastone solid organic acid which comprises at least one chelating acid fromthe group consisting of alpha- and beta-amino acids andhydroxycarboxylic acids, by introducing each of the at least one metalcompound and the at least one solid organic compound in particulate forminto a fluid jet of a fluidized-bed opposed-jet mill operating withoutmilling media; and subjecting the solvent-free mixture to mechanicalstress in said fluidized-bed opposed-jet mill which is sufficient forcausing mechanical activation of at least one of the at least one metalcompound and the at least one solid organic acid by particle collisionevents within a reaction space formed in a jet region of the fluid jetwhich is sufficient for a solid-state reaction to form metal chelateparticles wherein 90% of the metal chelate particles have a diameter ofnot more than 15 μm and 50% of the metal chelate particles have adiameter of not more than 5 μm.
 2. The process as claimed in claim 1,wherein the fluidized bed and the reaction space is formed in a fluidstream section in a crossing region of a jet direction of at least twofluid nozzles.
 3. The process as claimed in claim 1, wherein thefluidized-bed opposed-jet mill is operated at flow velocities rangingfrom about 300 to 1000 m/s, and at a milling gas pressure ranging fromabout 5 to 10 bar.
 4. The process as claimed in claim 1 wherein each ofthe at least one metal compound and the at least one solid organic acidare transported by a transport device into a milling chamber and reachthe reaction space in an interior of the milling chamber in free fall.5. The process as claimed in claim 1 wherein a fluid in the fluid jet isa gas selected from the group consisting of air, nitrogen, argon, carbondioxide, and steam, in each case either individually or in admixture. 6.The process as claimed in claim 1 wherein the at least one metalcompound is a metal carbonate or metal oxalate.
 7. The process asclaimed in claim 1 wherein the at least one metal compound contains atleast one metal or a mixture of metals selected from the groupconsisting of zinc (Zn), copper (Cu), manganese (Mn), selenium (Se),iron (Fe), calcium (Ca), magnesium (Mg), nickel (Ni), cobalt (Co),vanadium (V), chromium (Cr) and molybdenum (Mo).
 8. The process asclaimed in claim 1 wherein the subjecting step is performed such that99.9% of the metal chelate particles have a diameter of not more than 25μm.